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Background: Diffuse large B‐cell lymphoma (DLBCL) is the most common form of lymphoma. European guidelines recommend FDG‐PET/CT for staging and end of treatment (EOT) response assessment, mid‐treatment response assessment is optional. We compared the Lugano classification and PET Response Criteria In Solid Tumours (PERCIST) for FDG‐PET/CT response assessment in DLBCL head‐to‐head. Methods: We retrospectively included patients with DLBCL who underwent first‐line R‐CHOP(‐like) therapy (2013−2020). Interim and EOT FDG‐PET/CT response were reevaluated using the Lugano classification and PERCIST. Response was dichotomized into complete metabolic response (CMR) versus non‐CMR (interim and EOT) and responders versus nonresponders (interim only). The cutoff for nonresponse at interim was a Deauville score of 5 (DS5) with the Lugano classification and a partial metabolic response with ≤66% reduction in SULpeak using PERCIST (PERCIST66). Results: In multivariable Cox regression (N = 170), DS5 at interim, PERCIST66 at interim, non‐CMR at EOT with the Lugano classification and non‐CMR at EOT with PERCIST were predictive of progression‐free survival (PFS). The Lugano classification and PERCIST agreed perfectly at interim and EOT and with 98.4% for the identification of nonresponders at interim. The accuracy for predicting events within 2 years of diagnosis was 84.2% for DS‐5 at interim, 87.6% for PERCIST66 at interim, 86% for non‐CMR with the Lugano classification at EOT and 83.3% for non‐CMR with PERCIST at EOT. Conclusion: The Lugano classification and PERCIST were equally predictive of PFS. Nonresponse at interim and non‐CMR at EOT were predictive of poor PFS with comparable accuracy for predicting events within 2 years. [ABSTRACT FROM AUTHOR]

We evaluated the cost-effectiveness of 2-[18F]FDG-PET/CT compared to CE-CT for response monitoring in metastatic breast cancer (MBC) patients. The study included 300 biopsy-verified MBC patients treated at Odense University Hospital (Denmark). CE-CT was used in 144 patients, 83 patients underwent 2-[18F]FDG-PET/CT, and 73 patients received a combination of both. Hospital resource-based costs (2007–2019) were adjusted to the 2019 level. The incremental cost-effectiveness ratio (ICER) was calculated by comparing average costs per patient and gained survival with CE-CT. During a median follow-up of 33.0 months, patients in the 2-[18F]FDG-PET/CT group had more short admissions (median 6 vs. 2) and fewer overnight admissions (5 vs. 12) compared to the CE-CT group. The mean total cost per patient was €91,547 for CE-CT, €83,965 for 2-[18F]FDG-PET/CT, and €165,784 for the combined group. The ICER for 2-[18F]FDG-PET/CT compared to CE-CT was €-527/month, indicating gaining an extra month of survival at a lower cost (€527). 2-[18F]FDG-PET/CT was more cost-effective in patients with favorable prognostic factors (oligometastatic or estrogen receptor-positive disease), while CE-CT was more cost-effective in poor prognosis patients (liver/lung metastases or performance status ≥ 2 at baseline). In conclusion, our study suggests that 2-[18F]FDG-PET/CT is a cost-effective modality for response monitoring in metastatic breast cancer. [ABSTRACT FROM AUTHOR]

We evaluated the cost-effectiveness of 2-[18F]FDG-PET/CT compared to CE-CT for response monitoring in metastatic breast cancer (MBC) patients. The study included 300 biopsy-verified MBC patients treated at Odense University Hospital (Denmark). CE-CT was used in 144 patients, 83 patients underwent 2-[18F]FDG-PET/CT, and 73 patients received a combination of both. Hospital resource-based costs (2007–2019) were adjusted to the 2019 level. The incremental cost-effectiveness ratio (ICER) was calculated by comparing average costs per patient and gained survival with CE-CT. During a median follow-up of 33.0 months, patients in the 2-[18F]FDG-PET/CT group had more short admissions (median 6 vs. 2) and fewer overnight admissions (5 vs. 12) compared to the CE-CT group. The mean total cost per patient was €91,547 for CE-CT, €83,965 for 2-[18F]FDG-PET/CT, and €165,784 for the combined group. The ICER for 2-[18F]FDG-PET/CT compared to CE-CT was €-527/month, indicating gaining an extra month of survival at a lower cost (€527). 2-[18F]FDG-PET/CT was more cost-effective in patients with favorable prognostic factors (oligometastatic or estrogen receptor-positive disease), while CE-CT was more cost-effective in poor prognosis patients (liver/lung metastases or performance status ≥ 2 at baseline). In conclusion, our study suggests that 2-[18F]FDG-PET/CT is a cost-effective modality for response monitoring in metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Bland–Altman limits of agreement are very popular in method comparison studies on quantitative outcomes. However, a straightforward application of Bland–Altman analysis requires roughly normally distributed differences, a constant bias, and variance homogeneity across the measurement range. If one or more assumptions are violated, a variance-stabilizing transformation (e.g., natural logarithm, square root) may be sufficient before Bland–Altman analysis can be performed. Sometimes, fractional polynomial regression has been used when the choice of variance-stabilizing transformation was unclear and increasing variability in the differences was observed with increasing mean values. In this case, regressing the absolute differences on a function of the average and applying fractional polynomial regression to this end were previously proposed. This review revisits a previous inter-rater agreement analysis on the Agatston score for coronary calcification. We show the inappropriateness of a straightforward Bland–Altman analysis and briefly describe the nonparametric limits of agreement of the original investigation. We demonstrate the application of fractional polynomials, use the Stata packages fp and fp_select, and discuss the use of degree-2 (the default setting) and degree-3 fractional polynomials. Finally, we discuss conditions for evaluating the appropriateness of nonstandard limits of agreement. [ABSTRACT FROM AUTHOR]

Purpose: The preferred nuclear medicine method for identification of hyperfunctioning parathyroid glands in hyperparathyroidism (HPT) develops continuously in relation to the technological progress. Diagnostic methods based on PET/CT have during recent years evolved with new tracer possibilities competing with traditional scintigraphic methods. This investigation is a head-to-head comparison of Tc-99m-sestamibi SPECT/CT gamma camera scintigraphy (sestamibi SPECT/CT) and C-11-L-methionin PET/CT imaging (methionine PET/CT) for preoperative identification of hyperfunctioning parathyroid glands. Procedures: The study is a prospective cohort study including 27 patients diagnosed with primary hyperparathyroidism (PHPT). Two nuclear medicine physicians assessed all examinations independently and blinded. All scanning assessments were matched to the final surgical diagnosis as confirmed by histopathology. Biochemical monitoring of the therapeutical effects was performed preoperatively by PTH-measurements and followed postoperatively for up to 12 months. Comparisons were made for differences in sensitivity and positive predictive value (PPV). Results: Twenty-seven patients (18 females, 9 males; mean age (range): 58.9 years (34.1–79)) were enrolled into the study. The 27 patients had a total of 33 identified sites of lesions of which 28 (85%) turned out to be histopathological verified hyperfunctioning parathyroid glands. The sensitivity and PPV for sestamibi SPECT/CT were 0.71 and 0.95; that of methionine PET/CT was 0.82 and 1, respectively. Both sensitivity and PPV were slightly lower for sestamibi SPECT/CT than for methionine PET PET/CT (−0.11, 95% confidence interval (95% CI): −0.29 to 0.08; −0.05, 95% CI: −0.14 to 0.04, respectively), but not to a statistically significant extent (p=0.38 and p=0.31). The sensitivity and PPV for diagnostic CT were 0.64 (95% CI: 0.44 to 0.81) and 1 (95% CI: 0.81 to 1). Conclusions: Methionine PET/CT performed comparable to sestamibi SPECT/CT with respect to identification and localization of hyperfunctioning parathyroid glands prior to surgery. [ABSTRACT FROM AUTHOR]

Method comparison studies comprised simple scatterplots of paired measurements, a 45-degree line as benchmark, and correlation coefficients up to the advent of Bland–Altman analysis in the 1980s. The Agatston score for coronary calcification is based on computed tomography of the heart, and it originated in 1990. A peculiarity of the Agatston score is the often-observed skewed distribution in screening populations. As the Agatston score has manifested itself in preventive cardiology, it is of interest to investigate how reproducibility of the Agatston score has been established. This review is based on literature findings indexed in MEDLINE/PubMed before 20 November 2021. Out of 503 identified articles, 49 papers were included in this review. Sample sizes were highly variable (10–9761), the main focus comprised intra- and interrater as well as intra- and interscanner variability assessments. Simple analysis tools such as scatterplots and correlation coefficients were successively supplemented by first difference, later Bland–Altman plots; however, only very few publications were capable of deriving Limits of Agreement that fit the observed data visually in a convincing way. Moreover, several attempts have been made in the recent past to improve the analysis and reporting of method comparison studies. These warrant increased attention in the future. [ABSTRACT FROM AUTHOR]

The area under the receiver operating characteristics curve is a popular measure of the overall discriminatory power of a continuous variable used to indicate the presence of an outcome of interest, such as disease or disease progression. In clinical practice, the use of cut-off points as benchmark values for further treatment planning is greatly appreciated, despite the loss of information that such a dichotomization implies. Optimal cut-off points are often derived from fixed sample size studies, and the aim of this study was to investigate the convergence behavior of optimal cut-off points with increasing sample size and to explore a heuristic and path-based algorithm for cut-off point determination that targets stagnating cut-off point values. To this end, the closest-to-(0,1) criterion in receiver operating characteristics curve analysis was used, and the heuristic and path-based algorithm aimed at cut-off points that deviated less than 1% from the cut-off point of the previous iteration. Such a heuristic determination stopped after only a few iterations, thereby implicating practicable sample sizes; however, the result was, at best, a rough estimate of an optimal cut-off point that was unbiased and positively and negatively biased for a prevalence of 0.5, smaller than 0.5, and larger than 0.5, respectively. [ABSTRACT FROM AUTHOR]

Staging carcinoma of the uterine cervix (CCU) by FIGO-2018 suggests stage migration of FIGO-2009 stage I-III patients with lymph node metastasis into FIGO-2018 stage IIIC. We aimed to investigate the prognostic value of lymph node metastases identified by imaging. We enrolled all patients with biopsy-verified CCU from 2007 to 2016 at Odense University Hospital, Denmark. FDG-PET/CT and MRI were performed before clinical examination in general anesthesia. Disease-specific mortality was compared between women with lymph node-positive and lymph node-negative imaging. In total, 488 patients underwent clinical staging according to FIGO-2009. Lymph node-positive imaging was identified in 146 (30%) patients: 0/36 (0%) in stage IA, 22/195 (11%) in IBI, 14/30 (47%) in IB2, 70/164 (43%) in II and 40/63 (63%) in III. The 5-year cumulative incidence of death due to CCU lymph node-negative vs. lymph node-positive patients was 0.8% vs. 7.1% (p = 0.034) in stage IBI, 0% vs. 34.5% (p = 0.003) in stage IB2, 15.1% vs. 41.4% (p < 0.0001) in stage II, and 33.3% vs. 46.6% (p = 0.28) in stage III by FIGO-2009. One of three women with FIGO-2009 stage I-III CCU had suspected lymph node metastasis on imaging and is upstaged to stage IIIC according to FIGO-2018. The cancer-specific mortality by CCU was significantly lower in the lymph node-negative women stages IBI-II, thus supporting stage migration due to suspected lymph node metastasis. However, the exact prognostic value within stage IIIC is challenged, and future revision of FIGO stages may include new sub-stages. • One-third of women with CCU were upstaged to stage IIIC by the FIGO-2018 staging system. • Lymph node involvement by modern imaging is a significant prognostic factor in stages I-II but not in stage III. • The prognostic properties within stage IIIC subgroups stratified by tumor size are variable. • The sensitivity of lymph node imaging is low in early-stage CCU, and histological verification is warranted. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are resistant to conventional therapy and present a major clinical challenge since they are responsible for the relapse of many cancers, including non-small cell lung cancer (NSCLC). Hence, future successful therapy should also eradicate CSCs. Auger electrons have demonstrated promising therapeutic potential and can induce DNA damage while sparing surrounding cells. Here, we sort primary patient-derived NSCLC cells based on their expression of the CSC-marker CD44 and investigate the effects of cisplatin and a thymidine analog (deoxyuridine) labeled with an Auger electron emitter (125I). We show that the CD44+ populations are more resistant to cisplatin than the CD44− populations. Interestingly, incubation with the thymidine analog 5-[125I]iodo-2′-deoxyuridine ([125I]I-UdR) induces equal DNA damage, G2/M cell cycle arrest, and apoptosis in the CD44− and CD44+ populations. Our results suggest that Auger electron emitters can also eradicate resistant lung cancer CD44+ populations. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a systematic review of articles on PET imaging of carotid atherosclerosis with emphasis on clinical usefulness and comparison with other imaging modalities. Methods: Research articles reporting carotid artery PET imaging with different radiotracers until 30 November 2018 were systematically searched for in Medline/PubMed, Scopus, Embase, Google Scholar, and Cochrane Library. Duplicates were removed, and editorials, case studies, and investigations on feasibility or reproducibility of PET imaging and of patients with end-stage diseases or immunosuppressive medications were omitted. After quality assessment of included articles using Joanna Briggs Institute checklists, all eligible articles were reviewed. Results: Of 1718 primary hits, 53 studies comprising 4472 patients, aged 47–91 years (78.8% males), were included and grouped under the following headlines: diagnostic performance, risk factors, laboratory findings, imaging modalities, and treatment. 18F-fluorodeoxyglucose (FDG) (49/53) and 18F-sodium fluoride (NaF) (5/53) were the most utilized tracers to visualize carotid wall inflammation and microcalcification, respectively. Higher carotid FDG uptake was demonstrated in patients with than without symptomatic carotid atherosclerosis. Normal carotid arteries presented with the lowest FDG uptake. In symptomatic atherosclerosis, carotid arteries ipsilateral to a cerebrovascular event had higher FDG uptake than the contralateral carotid artery. FDG uptake was significantly associated with age, male gender, and body mass index in healthy individuals, and in addition with arterial hypertension, hypercholesterolemia, and diabetes mellitus in patients. Histological assessment indicated a strong correlation between microcalcification and NaF uptake in symptomatic patients. Histological evidence of calcification correlated inversely with FDG uptake, which was associated with increased macrophage and CD68 count, both accounting for increased local inflammatory response. Conclusion: FDG-PET visualizes the inflammatory part of carotid atherosclerosis enabling risk stratification to a certain degree, whereas NaF-PET seems to indicate long-term consequences of ongoing inflammation by demonstrating microcalcification allowing discrimination of atherosclerotic from normal arteries and suggesting clinically significant carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

When studying illnesses that cause disturbance in volume such as lymphedema, reliable quantification of tissue volume is important. Lymphedema results in swelling and enlargement of extremities and can be both physically and psychologically stressful to the patient. Experiments in rodent models provide a cost-effective research platform and are important for preclinical research on lymphedema. When performing such research, it can be crucial to measure the changes in tissue volume. Researchers must ensure that the risk of measurement error, when measuring the tissue volume, is as low as possible. The main goal of this article was to perform a comprehensive examination of the intra- and interrater agreement and hereby assess the risk of measurement error when using microcomputed tomography (µCT) images to measure hindlimb volume. We examined the agreement between four raters with different levels of prior experience and found that the risk of measurement error is extremely low when using this method. The main limitation of this method is that it is relatively expensive and time-consuming. The main advantages of this method are that it is easily learned and that it has a high intra- and interrater agreement, even for raters with no prior measuring experience. [ABSTRACT FROM AUTHOR]

Positron emission tomography/x-ray computed tomography (PET/CT) has long been discussed as a promising modality for response evaluation in cancer. When designing respective clinical trials, several design issues have to be addressed, especially the number/timing of PET/CT scans, the approach for quantifying metabolic activity, and the final translation of measurements into a rule. It is unclear how well these issues have been tackled in quest of an optimised use of PET/CT in response evaluation. Medline via Ovid and Science Citation Index via Web of Science were systematically searched for articles from 2015 on cancer patients scanned with PET/CT before and during/after treatment. Reports were categorised as being either developmental or evaluative, i.e. focusing on either the establishment or the evaluation of a rule discriminating responders from non-responders. Of 124 included papers, 112 (90 %) were accuracy and/or prognostic studies; the remainder were response-curve studies. No randomised controlled trials were found. Most studies were prospective (62 %) and from single centres (85 %); median number of patients was 38.5 (range 5-354). Most (69 %) of the studies employed only one post-baseline scan. Quantification was mainly based on SUVmax (91 %), while change over time was most frequently used to combine measurements into a rule (79 %). Half of the reports were categorised as developmental, the other half evaluative. Most development studies assessed only one element (35/62, 56 %), most frequently the choice of cut-off points (25/62, 40 %). In summary, the majority of studies did not address the essential open issues in establishing PET/CT for response evaluation. Reasonably sized multicentre studies are needed to systematically compare the many different options when using PET/CT for response evaluation. [ABSTRACT FROM AUTHOR]

Background: It is essential to have an accurate assessment of the renal function of patients with chronic kidney disease to monitor, treat, and predict further development of the condition. Measurement of renal function in terms of glomerular filtration rate (GFR) requires either urine or blood sampling, but especially in children, more simple methods of measurement are preferable. The main objective of this study was to examine if the estimated GFR (eGFR) calculated with different cystatin‐C‐based equations was comparable to the GFR measured by a radiotracer (mGFR) in pediatric patients. Methods: In this retrospective study, 28 pediatric patients contributed with 73 pairs of measurements collected within 5 years. Bland–Altman Limits of Agreement were used to evaluate the performance and accuracy of two different cystatin‐C‐based estimates, the CKiDCrea‐CysC and the CKiDU25 respectively, compared to an mGFR based on plasma clearance of technetium‐99m‐diethylenetriaminepentaacetic acid or chromium‐51‐ethylenediaminetetraacetic acid. Results: Using the CKiDCrea‐CysC equation, 58.9% of the datasets were within P10 and 87.7% were within P30. The mean difference was 4.8 mL/min/1.73m2 (standard deviation: 8.5 mL/min/1.73m2) and tended to overestimate GFR and thereby overrate the kidney function within the entire GFR range. Using the CKiDU25 equation, 53.4% were within P10 and 93.2% within P30. The mean difference was −2.9 mL/min/1.73m2 (standard deviation: 8.4 mL/min/1.73m2), but the difference varied with the GFR value. Conclusions: A cystatin‐C‐based eGFR provides a viable substitute for monitoring renal function in pediatric patients with chronic kidney disease. However, it has a lower accuracy than mGFR and can therefore not replace mGFR in clinical use. [ABSTRACT FROM AUTHOR]

Purpose: We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: We performed FDG-PET/CT in 23 patients (mean age 63.7 years, range 50–78, 17 females) diagnosed with AD (n = 15) or MCI (n = 8) during a six-month period in 2014. Ten neurologically healthy individuals (HIs) (mean age 62.5 years, range 43–75, 5 females) served as controls. A neuroimaging expert provided visual assessment of diaschisis. The total hemispheric glucose metabolism ratio (THGr) was calculated, and with area-under the curve of receiver operating characteristics (AUC-ROC) we generated a "Network Diaschisis Test (NDT)". Results: The qualitative detection of cerebral (Ce) and cerebellar (Cb) diaschisis was 7/15 (47%), 0/8 (0%), and 0/10 (0%) in AD, MCI, and HI groups, respectively. Median cerebral THGr was 0.68 (range 0.43–0.99), 0.86 (range 0.64–0.98), and 0.95 (range 0.65–1.00) for AD, MCI, and HI groups, respectively (p = 0.04). Median cerebellar THGr was, respectively, 0.70 (range 0.18–0.98), 0.70 (range 0.48–0.81), and 0.84 (range 0.75–0.96) (p = 0.0138). A positive NDT yielded a positive predictive value of 100% for the presence of AD or MCI and a 86% negative predictive value for healthy brain. Moreover, the diagnostic manifestation of THGr between MCI and AD led to a positive predictive value of 100% for AD, but a negative predictive value of 42.9% for MCI. Conclusion: Patients with AD or MCI had more pronounced diaschisis, lateralized hemispheric glucose metabolism and lower THGr compared to healthy controls. The NDT distinguished AD and MCI patients from HIs, and AD from MCI patients with a high positive predictive value and moderate and low negative predictive values. THGr can be a straightforward source of investigating neuronal network diaschisis in AD and MCI and in other cerebral diseases, across institutions. [ABSTRACT FROM AUTHOR]

Background Computed tomography (CT) technology is rapidly evolving and software solution developed to optimize image quality and/or lower radiation dose. Purpose To investigate the influence of adaptive statistical iterative reconstruction (ASIR) at different radiation doses in coronary CT angiography (CCTA) in detailed image quality. Material and Methods A total of 160 CCTA were reconstructed as follows: 55 scans with filtered back projection (FBP) (650 mA), 51 scans (455 mA) with 30% ASIR (ASIR30), and 54 scans (295 mA) with 60% ASIR (ASIR60). For each reconstruction, subjective image quality was assessed by five independent certified cardiologists using a visual grading analysis (VGA) with five predefined image quality criteria consisting of a 5-point scale. Objective measures were contrast, noise, and contrast-to-noise ratio (CNR). Results The CTDIvol resulted in 10.3 mGy, 7.4 mGy, and 4.6 mGy for FBP, ASIR30, and ASIR60, respectively. Homogeneity of the left ventricular lumen was the sole aspect in which reconstruction algorithms differed with a decreasing effect for ASIR60 compared to FBP (estimated odds ratio [OR] = 0.49 [95% confidence interval (CI) = 0.32-0.76; P = 0.001]). Decreased sharpness and spatial- and low-contrast resolutions were observed when using ASIR instead of FBP, but differences were not statistically significant. Concerning objective measurements, noise increased significantly for ASIR30 (OR = 1.08; 95% CI = 1.02-1.14; P = 0.006) and ASIR60 (OR = 1.06; 95% CI = 1.01-1.12; P = 0.034) compared to FBP. Conclusion ASIR significantly decreased the subjectively assessed homogeneity of the left ventricular lumen and increased the objectively measured noise compared to FBP. Considering these results, ASIR at a reduced radiation dose should be implemented with caution. [ABSTRACT FROM AUTHOR]

Cystatin C (CysC) is known to be related to cardiovascular disease (CVD), including the presence and severity of coronary artery disease (CAD) and future clinical events. In this study, the association between CysC levels and (1) coronary artery calcification (CAC) in asymptomatic individuals from the general population as well as (2) different subgroups of patients with suspected or definite acute myocardial infarction (MI) was investigated. CysC levels were measured in serum from asymptomatic individuals as part of a screening study for CAC using non-contrast cardiac CT scan (N = 1039) as well as in subgroups of hospitalized patients with a suspected MI (N = 769). CysC was not associated with CAC in asymptomatic individuals after adjusting for relevant risk factors. No difference in CysC levels was observed between patients with type 1 MI (1.07 mg/L) and patients with normal troponin (with or without prior CAD: 1.14 and 1.01 mg/L, respectively). However, patients with type 2 MI and patient subgroups with elevated troponin but without MI had significantly higher CysC levels (1.24, 1.23 and 1.31 mg/L), even after adjusting for other risk factors. CysC was not associated with CAC in middle-aged asymptomatic individuals from the general population. Furthermore, CysC levels were found to be significantly lower in patients with type 1 MI compared to patients with type 2 MI and patients with elevated troponins but without MI. Thus, in two independent and clinically different populations, no association between CysC and coronary atherosclerotic manifestations could be demonstrated. [ABSTRACT FROM PUBLISHER]

The diagnostic accuracy of up-front 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for detecting cervical lymph node metastases in patients with T1–T2 oral squamous cell carcinoma is reported with large discrepancies across the literature. We investigated the sensitivity, specificity, positive and negative predictive value, and accuracy of up-front PET/CT for detecting cervical lymph node metastases in this patient group and compared the performance to magnetic resonance imaging (MRI). In this prospective cohort study, 76 patients with T1–T2 oral squamous cell carcinoma underwent an up-front PET/CT and MRI at the Odense University Hospital from September 2013 to February 2016. Sentinel node biopsy and elective neck dissection were used for histopathological verification of the imaging modalities. Up-front PET/CT was significantly more sensitive than neck MRI (74% vs. 27%, p = 0.0001), but less specific (60% vs. 88%, p = 0.001). The accuracy of PET/CT and neck MRI was comparable (66% vs. 63%, p = 0.85), the PPV was slightly in favor of neck MRI (56% vs. 62%, p = 0.73), the NPV was slightly in favor of PET/CT (77% vs. 63%, p = 0.16). Neither PET/CT nor neck MRI should stand alone for N-staging T1–T2 oral cavity cancer. [ABSTRACT FROM AUTHOR]

Background: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG-PET/CT measurements, illuminating the possibility of early trial termination which implicates significant potential time and resource savings. Methods: Primary lesion maximum standardised uptake value (SUVmax) was determined twice from preoperative FDG-PET/CTs in 45 ovarian cancer patients. Differences in SUVmax were assumed to be normally distributed, and sequential one-sided hypothesis tests on the population standard deviation of the differences against a hypothesised value of 1.5 were performed, employing an alpha spending function. The fixed-sample analysis ( N = 45) was compared with the group-sequential analysis strategies comprising one (at N = 23), two (at N = 15, 30), or three interim analyses (at N = 11, 23, 34), respectively, which were defined post hoc. Results: When performing interim analyses with one third and two thirds of patients, sufficient agreement could be concluded after the first interim analysis and the final analysis. Other partitions did not suggest early stopping after adjustment for multiple testing due to one influential outlier and our small sample size. Conclusions: Group-sequential testing may enable early stopping of a trial, allowing for potential time and resource savings. The testing strategy must, though, be defined at the planning stage, and sample sizes must be reasonably large at interim analysis to ensure robustness against single outliers. Group-sequential testing may have a place in accuracy and agreement studies. [ABSTRACT FROM AUTHOR]

Background and aims High serum calcium-phosphate levels are associated with increased risk of cardiovascular disease (CVD) in patients with chronic kidney disease. Recent studies have demonstrated this relationship also in subjects with normal kidney function. Our aim was to examine whether calcium-phosphate metabolism is associated with the presence and extent of coronary artery calcification (CAC) in asymptomatic and apparently healthy individuals. Methods Serum samples from 1088 randomly recruited middle-aged men and women without known CVD and diabetes (DM), from the general population, were analysed for total calcium, phosphate, parathyroid hormone (PTH) and 25-hydroxyvitamin D (25(OH)D). CAC was measured by a non-contrast cardiac CT scan and categorised into four groups: 0, 1–99, 100–399, ≥400 Agatston units. The association of calcium-phosphate metabolism with CAC was evaluated by a multiple ordered logistic regression model. All the multiple regression analyses were performed in the entire cohort as well as in men and women separately. Results In the study population, 96% of the serum calcium values, 93% of the PTH values, 90% of the phosphate values, and only 64% of the 25(OH)D values were placed within the normal range. In men, the odds of being in a higher CAC category, i.e. having more severe CAC, increased by 30% when serum calcium concentration increased by 0.1 mmol/l (95% CI: 1.04–1.61, p = 0.019), independently of traditional cardiovascular risk factors. In women, no significant association between serum calcium and CAC was identified (OR 0.99, 95% CI: 0.81–1.21, p = 0.91). Neither phosphate, PTH nor 25(OH)D was significantly associated with CAC in men, in women or when performed in the entire cohort. Conclusions Serum calcium, even with values within normal range and independent of traditional risk factors, was significantly associated with CAC in asymptomatic and apparently healthy middle-aged men, but not in women. [ABSTRACT FROM AUTHOR]

Background: Management of the distal radius fracture (DRF) is to some extent based on radiographic characterization of fracture displacement. It remains unclear, however, if the measurements used to quantify displacement are accurate. Purpose: To quantify accuracy of two radiographic measurements: dorsal/volar tilt and fracture compression, measured indirectly as ulnar variance (UV), using radiostereometric analyses (RSA) as reference standard. Material and Methods: Twenty-one fresh frozen non-fractured human cadaveric forearms (right = 11, left = 10) were thawed and eligible for inclusion. The forearms were mounted on a custom made platform that allowed for controlled forearm rotation, and they underwent two rounds of imaging (both rounds consisted of RSA and radiographs). In round one, the non-fractured forearms were radiographed. In round two, artificial DRF's with compression and dorsal angulation were created and imaging procedures repeated. Change in tilt and UV between the non-fractured and later fractured forearms was defined as fracture-induced deformity. Deformity was measured radiographically and additionally calculated using RSA. Bland Altman analyses were used to estimate agreement between radiographically measured, and RSA calculated, fracture-induced deformity. Results: Our results indicated that radiographs underestimate the amount of fracture-induced deformity. Mean measured differences (bias) in dorsal tilt deformity between radiographs and RSA were -2.5° for both observers. The corresponding values for UV were -1.4 mm and -1.5 mm. Conclusion: Quantifying fracture-induced deformity on radiographs underestimated the actual deformity when compared to RSA calculated deformity. These findings suggest that clinicians, at least in part, base fracture management and potentially corrective surgery on inaccurate measurements. [ABSTRACT FROM AUTHOR]

Introduction: The studies that constitute the knowledge base of evidence based medicine represent only 5%-50% of patients seen in routine clinical practice. Therefore, whether the available evidence applies to the implementation of a particular service often remains unclear. Chronic obstructive pulmonary disease (COPD) is no exception.Methods: In this article, the effects of implementing a telemedicine intervention for COPD patients were analysed using data collected before, during, and after a randomised controlled trial (RCT).More specifically, regression techniques using robust variance estimators were used to analyse whether the use of telemedicine, patient age, and gender could explain the risk of readmission, length of hospital admission, and death during a five-year observation period.Results: Increased risk of readmission was significantly related to both use of telemedicine and increased age in three sub-periods of the study, whereas women showed a more pronounced risk of readmission than men only during and after the RCT period. The number of days admitted to hospital was higher for patients using telemedicine and being of older age. Risk of death during the observation period was decreased for patients using telemedicine and for female patients and increased for elderly patients. No interaction between intervention and time period was observed.Statistically significant relationships were identified between use of telemedicine and risk of readmission, days admitted to hospital, and death.Discussion: Research on effect modification in telemedicine is essential in designing future implementation of interventions as it cannot be taken for granted that effectiveness follows from efficacy. [ABSTRACT FROM AUTHOR]

Objective The main objective of this study was to investigate the association between two markers of low-grade inflammation; soluble urokinase plasminogen activator receptor (suPAR) and high-sensitive C-reactive protein (hs-CRP); and coronary artery calcification (CAC) score detected by cardiac computed tomography (CT) scan. Design A cross sectional study of 1126 randomly sampled middle-aged men and women. Methods CAC score was measured by a non-contrast cardiac CT scan and total 10-year cardiovascular mortality risk was estimated using the Systematic Coronary Risk Evaluation (SCORE). Plasma samples were analysed for suPAR and hs-CRP. The association of suPAR and hs-CRP to CAC was evaluated by logistic regression analyses adjusting for categorised SCORE. The additive effect of suPAR to SCORE was evaluated by comparing area under curve (AUC) and net reclassification improvement (NRI). Results The odds of being in a higher CAC category, i.e. having more severe CAC, increased 16% (odds ratio (OR) 1.16, p = 0.02) when plasma suPAR concentration increased 1 ng/ml, and this was more pronounced in women (OR 1.30, p = 0.01) than in men (OR 1.15, p = 0.05). In comparison, hs-CRP was not associated with CAC category (OR 1.00, p = 0.90). When adding suPAR to categorised SCORE, AUC increased from 0.66 to 0.70 ( p = 0.04) in women and from 0.65 to 0.68 ( p = 0.03) in men. NRI was significant in men (NRI 19.3%, 95% CI 6.1–32.6, p = 0.004) as well as in women (NRI 20.8%, 95%CI 1.0–40.7, p = 0.04), without significant gender difference. Conclusions suPAR, but not hs-CRP, appeared to be associated with CAC score independently of SCORE. The association was strongest in women. [ABSTRACT FROM AUTHOR]

Trading cards for various sports and a range of other subjects such as architecture, animals, hobbies, and war have been in existence since the late nineteenth century and still enjoy great popularity. Two of the most prominent examples are baseball cards in the U.S. and football cards in Europe. Three strategies for collecting European football trading cards were investigated for two different groups: either a single collector or two collectors joining forces. An activity is proposed in which students use a simulation to compute the factor by which the number of trading cards bought exceeds the number to be collected. This enables them to estimate the expected costs of completing a collection of trading cards. The overall expected costs vary considerably, depending on the strategy used. Savings for a team of two collectors as opposed to a single collector are indicated. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Diagnostic studies are typically studies with two endpoints, sensitivity and specificity. To define the success of a diagnostic study, results for these two endpoints have to be combined in an appropriate manner. Study Design and Setting: Identification of criteria to define the success of a diagnostic study on a single binary test and investigation of common statistical approaches in relation to these criteria. Results: Three criteria for defining the overall success of a diagnostic study could be identified: a strong criterion, a liberal criterion, and a weak criterion. The strong criterion can be implemented by comparing the lower bounds of the confidence intervals for sensitivity and specificity with prespecified target values, as is typically done in many diagnostic studies. The liberal criterion allows a clinically meaningful compensation between sensitivity and specificity and can be implemented in different ways. If the liberal criterion is applied instead of the strong criterion, this can lead to a substantial reduction in the sample size required for a diagnostic study. The weak criterion is not very adequate for defining the success of a diagnostic study. Conclusion: When planning and analyzing diagnostic studies, the criterion to define the success of the study should be clearly prespecified. The results of the statistical approach taken should be interpreted in accordance with this criterion. This ensures coherence of results and prevents unnecessarily large sample sizes. The liberal criterion should be paid more attention to in the future. [Copyright &y& Elsevier]

Scand J Caring Sci; 2011; 25; 383-393 There is no systematic identification of parents with excessive alcohol use who have a child admitted to hospital. Children in families with excessive alcohol issues form a high risk group as substantial alcohol consumption has a damaging influence on a child emotionally, cognitively, socially and physically. Alcohol consumption is a sensitive issue, and health staff needs knowledge, qualifications and adequate training in communicating with parents about this taboo. During 1 year, screening and brief intervention (SBI) was accomplished, including health staff conducting dialogues with parents of a hospitalized child using motivational interviewing (MI) and screening for risky alcohol behaviour by Cut down, Annoyance from others, feel Guilty, Early-morning Craving (CAGE)-C. Data were analysed by descriptive statistics, and relationships were tested with a statistical significance level of 0.05, using SPSS (version 16.0). Motivational dialogues with 779 parents were conducted by 43 staff members, and 11% of the parents were screened positive for risky alcohol behaviour. Drinking alcohol 4 days a week or more and drinking alcohol outside mealtimes were main risk factors. Parents' gender was the strongest predictor of screening positive and OR was 6.8 for men (CI 4.03-11.74) compared to women, p < 0.0001. An OR of 1.2 for parents' age (CI 1.02-1.42) indicates the risk of screening positive increases with age, p = 0.027. Brief intervention using CAGE-C and MI has proven successful in mapping parents' alcohol consumption patterns and in identifying parents with risky alcohol consumption habits. Health staff is able to manage health promotion and prevention when having the right competences and when being supervised. [ABSTRACT FROM AUTHOR]

Purpose: For certain cancer indications, the current patient evaluation strategy is a perfect but locally restricted gold standard procedure. If positron emission tomography/computed tomography (PET/CT) can be shown to be reliable within the gold standard region and if it can be argued that PET/CT also performs well in adjacent areas, then sample sizes in accuracy studies can be reduced.Procedures: Traditional standard power calculations for demonstrating sensitivities of both 80% and 90% are shown. The argument is then described in general terms and demonstrated by an ongoing study of metastasized prostate cancer.Results: An added value in accuracy of PET/CT in adjacent areas can outweigh a downsized target level of accuracy in the gold standard region, justifying smaller sample sizes.Conclusions: If PET/CT provides an accuracy benefit in adjacent regions, then sample sizes can be reduced and the conduct of trials accelerated, leading to earlier decisions on the use of PET/CT while exposing fewer patients and reducing overall costs. [ABSTRACT FROM AUTHOR]

In phase I oncology trials conducted over the past few decades, the maximum tolerated dose (MTD) has usually been estimated by the traditional escalation rule (TER), which traces back to 1973. In the meantime, new methods have been proposed which hope to estimate the true MTD more precisely than the TER while using less patients. In this simulation study, TER is compared with the accelerated titration dose design (ATD), two up-and-down designs (biased coin design, r-in-a-row (RIAR)), the maximum likelihood version of the continual reassessment method (CRML), and a Bayesian method that is implemented in the software Bayesian ADEPT (assisted decision-making in early phase trials). Each design was applied to 50 000 simulated studies. The designs were then compared for accuracy in detecting the true MTD (which is known here), while taking into account the average number of patients and toxicities per run. In terms of accuracy, ADEPT outperformed the other methods in the scenario with medium toxicity and was close to the best methods in the low and high toxic scenarios. The average number of patients needed per run was the lowest for TER in the scenario with low toxicity and for ADEPT in the remaining scenarios. The longer the escalation path to the target region of the MTD, the more the difference in the average number of patients per run pronounced between TER and ADEPT. TER induced least toxicities in all scenarios. ADEPT turned out to be quick and accurate in determining the MTD, while TER was the safest but least accurate method. CRML was as accurate as TER, and the up-and-down designs did not excel. Bayesian ADEPT is considered a valuable tool for the conduct of phase I dose-escalation trials in oncology, but careful preparation is indispensable before its practical use. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Cross‐sectional imaging supplements endoscopy in detecting disease manifestations in inflammatory bowel diseases (IBD). This study aimed to evaluate the accuracy of PET/MRI in a paediatric population suspected of IBD. This prospective study consecutively included patients aged 8–17 years under diagnostic evaluation for IBD. Forty‐three patients underwent a PET/MRI scan and subsequent ileocolonoscopy, of whom 26 patients diagnosed with IBD participated in a follow‐up scan, hereof 19 with Crohn's disease (CD), five with Ulcerative colitis and two with unclassified IBD. The results of PET alone, MRI alone, and PET/MRI combined were compared to a reference standard of endoscopy and histopathology. Of the 208 intestinal segments analysed, 109 showed inflammation, and 99 had no inflammation. In the per‐segment analysis PET had a sensitivity of 0.83 (95% CI 0.73–0.93), specificity of 0.59 (95% CI 0.47–0.71), and area under the receiver operating characteristic curve (AUROC) of 0.73 (95% CI 0.67–0.80). MRI had a sensitivity of 0.52 (95% CI 0.41–0.64), specificity 0.89 (95% CI 0.82–0.96), and AUROC of 0.72 (95% CI 0.66–0.77). PET/MRI had a sensitivity of 0.83 (95% CI 0.74–0.94), specificity of 0.57 (95% CI 0.44–0.69), and AUROC of 0.77 (95% CI 0.71–0.84). At follow‐up, PET and MRI scores decreased, and the change in MRI was able to identify patients with a clinical response. The accuracy of the PET/MRI scan in detecting inflammation in the terminal ileum and colon was moderate and not superior to either modality alone. With technological advances and combined reading, PET/MRI may still be valuable in selected cases. [ABSTRACT FROM AUTHOR]

Stress is a ubiquitous challenge in modern societies. Symptoms range from mood swings and cognitive impairment to autonomic symptoms. This study explores the link between work-related stress and the neurobiological element of brain processing, testing the hypothesis that patients with occupational stress have altered cerebral glucose consumption compared to healthy controls. The participants' present conditions were evaluated using an adapted WHO SCAN interview. Neural activity at rest was assessed by positron emission tomography (PET) with the glucose analogue [18F]fluorodeoxyglucose. Participants were genotyped for the Val158Met polymorphism of the COMT gene, believed to influence stress resilience. This study included 11 women with work-related stress and 11 demographically comparable healthy controls aged 28–62 years, with an average of 46.2 years. The PET scans indicated clusters of decreased glucose consumption primarily located in the white matter of frontal lobe sub-gyral areas in stress patients. COMT Val158Met polymorphism detection indicated no immediate relation of the homozygous alleles and stress resilience; however, healthy controls mainly had the heterozygous allele. In conclusion, the results support that work-related stress does affect the brain in the form of altered glucose metabolism, suggesting neurobiological effects could be related to white matter abnormalities rather than gray matter deterioration. Genotyping indicates a more complex picture than just that of the one type being more resilient to stress. Further studies recruiting a larger number of participants are needed to confirm our preliminary findings. [ABSTRACT FROM AUTHOR]

The authors reflect on the benefits of clinical nuclear imaging and the need for them to be analyzed economically. They mentions that with the increase in medical costs, it is necessary that diagnosis should be undertaken in the most efficient and low cost manner. They also cite the study of Stoffels and colleagues on the economic effects of single photon emission tomography (SPECT).

Measurement procedures are not error-free. Potential users of a measurement procedure need to know the expected magnitude of the measurement error in order to justify its use, in particular in health care settings. Gold standard procedures providing exact measurements for comparisons are often lacking. Consequently, scientific investigations of the measurement error are often based on using replicates. However, a standardized terminology (and partially also methodology) for such investigations is lacking. In this paper, we explain the basic conceptual approach of such investigations with minimal reference to existing terminology and describe the link to the existing general statistical methodology. This way, some of the key measures used in such investigations can be explained in a simple manner and some light can be shed on existing terminology. We encourage clearly conceptually distinguishing between investigations of the measurement error of a single measurement procedure and the comparison between different measurement procedures or observers. We also identify an unused potential for more advanced statistical analyses in scientific investigations of the measurement error. [ABSTRACT FROM AUTHOR]

Background: Current imaging modalities are often incapable of identifying nociceptive sources of low back pain (LBP). We aimed to characterize these by means of positron emission tomography/computed tomography (PET/CT) of the lumbar spine region applying tracers 18F‐fluorodeoxyglucose (FDG) and 18F‐sodium fluoride (NaF) targeting inflammation and active microcalcification, respectively. Methods: Using artificial intelligence (AI)‐based quantification, we compared PET findings in two sex‐ and age‐matched groups, a case group of seven males and five females, mean age 45 ± 14 years, with ongoing LBP and a similar control group of 12 pain‐free individuals. PET/CT scans were segmented into three distinct volumes of interest (VOIs): lumbar vertebral bodies, facet joints and intervertebral discs. Maximum, mean and total standardized uptake values (SUVmax, SUVmean and SUVtotal) for FDG and NaF uptake in the 3 VOIs were measured and compared between groups. Holm–Bonferroni correction was applied to adjust for multiple testing. Results: FDG uptake was slightly higher in most locations of the LBP group including higher SUVmean in the intervertebral discs (0.96 ± 0.34 vs. 0.69 ± 0.15). All NaF uptake values were higher in cases, including higher SUVmax in the intervertebral discs (11.63 ± 3.29 vs. 9.45 ± 1.32) and facet joints (14.98 ± 6.55 vs. 10.60 ± 2.97). Conclusion: Observed intergroup differences suggest acute inflammation and microcalcification as possible nociceptive causes of LBP. AI‐based quantification of relevant lumbar VOIs in PET/CT scans of LBP patients and controls appears to be feasible. These promising, early findings warrant further investigation and confirmation. [ABSTRACT FROM AUTHOR]

The Bland–Altman Limits of Agreement is a popular and widespread means of analyzing the agreement of two methods, instruments, or raters in quantitative outcomes. An agreement analysis could be reported as a stand-alone research article but it is more often conducted as a minor quality assurance project in a subgroup of patients, as a part of a larger diagnostic accuracy study, clinical trial, or epidemiological survey. Consequently, such an analysis is often limited to brief descriptions in the main report. Therefore, in several medical fields, it has been recommended to report specific items related to the Bland–Altman analysis. The present study aimed to identify the most comprehensive and appropriate list of items for such an analysis. Seven proposals were identified from a MEDLINE/PubMed search, three of which were derived by reviewing anesthesia journals. Broad consensus was seen for the a priori establishment of acceptability benchmarks, estimation of repeatability of measurements, description of the data structure, visual assessment of the normality and homogeneity assumption, and plotting and numerically reporting both bias and the Bland–Altman Limits of Agreement, including respective 95% confidence intervals. Abu-Arafeh et al. provided the most comprehensive and prudent list, identifying 13 key items for reporting (Br. J. Anaesth. 2016, 117, 569–575). An exemplification with interrater data from a local study accentuated the straightforwardness of transparent reporting of the Bland–Altman analysis. The 13 key items should be applied by researchers, journal editors, and reviewers in the future, to increase the quality of reporting Bland–Altman agreement analyses. [ABSTRACT FROM AUTHOR]

Objectives: To validate an AI system for standalone breast cancer detection on an entire screening population in comparison to first-reading breast radiologists. Materials and methods: All mammography screenings performed between August 4, 2014, and August 15, 2018, in the Region of Southern Denmark with follow-up within 24 months were eligible. Screenings were assessed as normal or abnormal by breast radiologists through double reading with arbitration. For an AI decision of normal or abnormal, two AI-score cut-off points were applied by matching at mean sensitivity (AIsens) and specificity (AIspec) of first readers. Accuracy measures were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and recall rate (RR). Results: The sample included 249,402 screenings (149,495 women) and 2033 breast cancers (72.6% screen-detected cancers, 27.4% interval cancers). AIsens had lower specificity (97.5% vs 97.7%; p < 0.0001) and PPV (17.5% vs 18.7%; p = 0.01) and a higher RR (3.0% vs 2.8%; p < 0.0001) than first readers. AIspec was comparable to first readers in terms of all accuracy measures. Both AIsens and AIspec detected significantly fewer screen-detected cancers (1166 (AIsens), 1156 (AIspec) vs 1252; p < 0.0001) but found more interval cancers compared to first readers (126 (AIsens), 117 (AIspec) vs 39; p < 0.0001) with varying types of cancers detected across multiple subgroups. Conclusion: Standalone AI can detect breast cancer at an accuracy level equivalent to the standard of first readers when the AI threshold point was matched at first reader specificity. However, AI and first readers detected a different composition of cancers. Clinical relevance statement: Replacing first readers with AI with an appropriate cut-off score could be feasible. AI-detected cancers not detected by radiologists suggest a potential increase in the number of cancers detected if AI is implemented to support double reading within screening, although the clinicopathological characteristics of detected cancers would not change significantly. Key Points: • Standalone AI cancer detection was compared to first readers in a double-read mammography screening population. • Standalone AI matched at first reader specificity showed no statistically significant difference in overall accuracy but detected different cancers. • With an appropriate threshold, AI-integrated screening can increase the number of detected cancers with similar clinicopathological characteristics. [ABSTRACT FROM AUTHOR]

Background: In 2011, as the first European country, Denmark introduced the non-organ-specific cancer patient pathway (CPP) for patients presenting with non-specific symptoms and signs of cancer (NSSC). The proportion of patients with cancer over time is unknown. Methods: A retrospective cohort study of all patients with a NSSC-CPP investigational course in the province of Funen to the Diagnostic Centre in Svendborg from 2014 to 2021 was performed to evaluate the proportion of patients with cancer and serious disease over time. Results: A total of 6698 patients were referred to the NSSC-CPP of which 20.2% had cancer. While the crude referral rate increased from 114 per 100,000 people in 2014 and stabilised to around 214 in 2017–2021, the cancer detection rate of the total yearly new cancers in Funen diagnosed through the NSSC-CPP in DC Svendborg increased from 3 to 6%. Conclusions: With now high and stable conversion and crude referral rates, the NSSC-CPP is one of the largest CPPs in Denmark as measured by the number of new cancer cases found. Similar urgent referral programmes in other countries might fill an unmet medical need for patients presenting with serious non-specific symptoms and signs of cancer in general practice. [ABSTRACT FROM AUTHOR]

We compared lesion-based sensitivity of dual-time-point FDG-PET/CT, bone scintigraphy (BS), and low-dose CT (LDCT) for detection of various types of bone metastases in patients with metastatic breast cancer. Prospectively, we included 18 patients with recurrent breast cancer who underwent dual-time-point FDG-PET/CT with LDCT and BS within a median time interval of three days. A total of 488 bone lesions were detected on any of the modalities and were categorized by the LDCT into osteolytic, osteosclerotic, mixed morphologic, and CT-negative lesions. Lesion-based sensitivity was 98.2% (95.4–99.3) and 98.8% (96.8–99.5) for early and delayed FDG-PET/CT, respectively, compared with 79.9% (51.1–93.8) for LDCT, 76.0% (36.3–94.6) for BS, and 98.6% (95.4–99.6) for the combined BS+LDCT. BS detected only 51.2% of osteolytic lesions which was significantly lower than other metastatic types. SUVs were significantly higher for all lesion types on delayed scans than on early scans (P<0.0001). Osteolytic and mixed-type lesions had higher SUVs than osteosclerotic and CT-negative metastases at both time-points. FDG-PET/CT had significantly higher lesion-based sensitivity than LDCT and BS, while a combination of the two yielded sensitivity comparable to that of FDG-PET/CT. Therefore, FDG-PET/CT could be considered as a sensitive one-stop-shop in case of clinical suspicion of bone metastases in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy. Methods: Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard. Results: [18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93–1.0), 0.88 (0.82–0.92), and 0.98 (95% CI 0.97–0.99), respectively. Conclusion: [18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer. Trial registration Clinical.Trials.gov. NCT03358589. Registered 30 November 2017—Retrospectively registered, http://www.ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

The Guidelines for Reporting Reliability and Agreement Studies (GRRAS) were proposed in 2011 to support transparent and accurate reporting. These studies may be conducted with the primary aim of estimating reliability and/or agreement itself, but are more often than not part of larger diagnostic accuracy studies, clinical trials, or epidemiological studies. As such, the study design may be compromised in terms of practicability issues, preventing the collection of sufficient results. We presented an example from a consultancy with a difficult mission and discussed five questions that concern the very nature of such a study (agreement vs. reliability; intra- vs. interrater), the rater population, explanatory factors in a multivariable model, and the statistical analysis strategy. Discussion of such basic methodological and statistical questions must take place before an investigation is started in order to ensure adequate data collection, to predict possible complications in the study, to plan sufficient statistical analyses, and to request timely assistance from an experienced statistician. GRRAS and its accompanying checklist of 15 items proved to be most helpful. Hopefully, our commentary will help improve the planning of agreement and reliability studies, which, in turn, will then be more focused, more appropriate, and more easily reported using GRRAS. [ABSTRACT FROM AUTHOR]

Background: Diagnostic accuracy studies aim to examine the diagnostic accuracy of a new experimental test, but do not address the actual merit of the resulting diagnostic information to a patient in clinical practice. In order to assess the impact of diagnostic information on subsequent treatment strategies regarding patient-relevant outcomes, randomized test-treatment studies were introduced. Various designs for randomized test-treatment studies, including an evaluation of biomarkers as part of randomized biomarker-guided treatment studies, are suggested in the literature, but the nomenclature is not consistent.Methods: The aim was to provide a clear description of the different study designs within a pre-specified framework, considering their underlying assumptions, advantages as well as limitations and derivation of effect sizes required for sample size calculations. Furthermore, an outlook on adaptive designs within randomized test-treatment studies is given.Results: The need to integrate adaptive design procedures in randomized test-treatment studies is apparent. The derivation of effect sizes induces that sample size calculation will always be based on rather vague assumptions resulting in over- or underpowered study results. Therefore, it might be advantageous to conduct a sample size re-estimation based on a nuisance parameter during the ongoing trial.Conclusions: Due to their increased complexity, compared to common treatment trials, the implementation of randomized test-treatment studies poses practical challenges including a huge uncertainty regarding study parameters like the expected outcome in specific subgroups or disease prevalence which might affect the sample size calculation. Since research on adaptive designs within randomized test-treatment studies is limited so far, further research is recommended. [ABSTRACT FROM AUTHOR]

Bystander defibrillation is associated with increased survival with good neurological outcome after out-of-hospital cardiac arrest (OHCA). Dispatch of lay responders could increase defibrillation rates, however, survival with good neurological outcome in these remain unknown. The aim was to compare long-term survival with good neurological outcome in bystander versus lay responder defibrillated OHCAs. This is a sub-study of the BOX trial, which included OHCA patients from two Danish tertiary cardiac intensive care units from March 2017 to December 2021. The main outcome was defined as 3-month survival with good neurological performance (Cerebral Performance Category of 1or 2, on a scale from 1 (good cerebral performance) to 5 (death or brain death)). For this study EMS witnessed OHCAs were excluded. Of the 715 patients, a lay responder arrived before EMS in 125 cases (16%). In total, 81 patients were defibrillated by a lay responder (11%), 69 patients by a bystander (10%) and 565 patients by the EMS staff (79%). The 3-month survival with good neurological outcome was 65% and 81% in the lay responder and bystander defibrillated groups, respectively (P = 0.03). In patients with OHCA, 3-month survival with good neurological outcome was higher in bystander defibrillated patients compared with lay responder defibrillated patients. [ABSTRACT FROM AUTHOR]

Background and aims: Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD). Methods: We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007–2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1–99, 100–399, ≥400) was investigated by ordered logistic regression adjusting for covariates. Results: The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009–1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935–1.074). There was no significant interaction between VKA treatment duration and age on CAC category. Conclusions: Adjusted for cardiovascular risk factors, VKA treatment–contrary to NOAC—was associated to higher CAC category. [ABSTRACT FROM AUTHOR]

Objective: Elective neck dissection in patients with salivary gland carcinoma and clinically negative lymph nodes is controversial. Reported proportion of occult nodal metastases vary with histological subtype, tumour classification and preoperative diagnostic methods. This is a systematic review and meta-analysis on the role of END in salivary gland carcinoma.Methods: A search in PubMed, Embase and Cochrane was performed. Original articles in English with data on tumour characteristics, clinical and pathological N-classification, and neck dissection were included. Reporting Items for Systematic Reviews and Meta-analyses were followed. Random effect modelling was performed to pool the data. Meta-analysis of proportions was performed for occult metastases overall, for T3/T4 versus T1/T2 tumours and for tumours with high-grade versus low-grade histology. Heterogeneity across studies was assessed with I-squared statistics.Results: We included 22 articles in the qualitative synthesis and meta-analysis. The pooled proportion of occult metastases was 21%. In patients with T3/T4 tumour, the pooled proportion of occult metastases was 36%, and in patients with high-grade histology, it was 34%. Most studies concluded that END should be performed in patients with advanced T-classification and high-grade histology tumours. Nine studies assessed occult metastases per level.Conclusion: The overall occult metastases proportion does not require END in all patients with salivary gland carcinoma. We recommend END in patients with high-grade or unknown histology or T3/T4 tumours. END should involve level II and III, and level I should be included in tumours in the submandibular gland, sublingual gland and minor oral salivary glands. [ABSTRACT FROM AUTHOR]

Purpose: To examine the diagnostic accuracy of spectral CT pulmonary angiography (S-CTPA) using ventilation-perfusions lung scintigraphy (V/Q-scan) as a reference standard in the diagnosis of acute or chronic pulmonary embolism (APE/CPE) and chronic thromboembolic pulmonary hypertension (CTEPH).Methods: PubMed, Embase, Scopus, and Web of Science were searched for the period from 1 Jan 2006 to 7 Feb 2019; eligible studies had > 10 patients over 18 years old, a diagnostic outcome of PE or CTEPH, and used V/Q scan as a reference standard. Bias and applicability were assessed using QUADAS-2 tools. Sensitivities, specificities, and predictive values were noted or calculated from available information. Meta-analysis employed a fixed-effects model of Mantel and Haenszel. Heterogeneity was assessed with I-squared statistics.Results: Four hundred ninety-three unique records were identified. Following screening by title, 53 studies were included in the abstract and full-text assessment. A total of six articles were included; four were suitable for a meta-analysis. Pooled sensitivity was 94.2% (95% CI, 88.3-100%), pooled specificity was 88.5% (95% CI, 81.3-95.6%), and positive and negative predictive values were 87.8% (95% CI, 80.3-95.4%) and 94.5% (95% CI, 89.3-99.7%), respectively.Conclusion: Data on S-CTPA for PE/CTEPH remains promising, but limited; only small studies with methodological issues are available. Evidence is best for CPE/CTEPH whereas no firm conclusions are possible for APE. There is a need for larger, prospective studies with a robust composite reference standard including state-of-the-art CTPA and V/Q-scans.Key Points: • S-CTPA has high sensitivity and specificity for perfusion defects in patients with PE or CPETH. • Methodological issues and diversity of reference standards were found in the small number of included studies. • There is a need for larger prospective studies with more robust composite reference standards. [ABSTRACT FROM AUTHOR]

The aim of diagnostic accuracy studies is to evaluate how accurately a diagnostic test can distinguish diseased from nondiseased individuals. Depending on the research question, different study designs and accuracy measures are appropriate. As the prior knowledge in the planning phase is often very limited, modifications of design aspects such as the sample size during the ongoing trial could increase the efficiency of diagnostic trials. In intervention studies, group sequential and adaptive designs are well established. Such designs are characterized by preplanned interim analyses, giving the opportunity to stop early for efficacy or futility or to modify elements of the study design. In contrast, in diagnostic accuracy studies, such flexible designs are less common, even if they are as important as for intervention studies. However, diagnostic accuracy studies have specific features, which may require adaptations of the statistical methods or may lead to specific advantages or limitations of sequential and adaptive designs. In this article, we summarize the current status of methodological research and applications of flexible designs in diagnostic accuracy research. Furthermore, we indicate and advocate future development of adaptive design methodology and their use in diagnostic accuracy trials from an interdisciplinary viewpoint. The term "interdisciplinary viewpoint" describes the collaboration of experts of the academic and nonacademic research. [ABSTRACT FROM AUTHOR]

Background: Non-expandable lung (NEL) has severe implications for patient symptoms and impaired lung function, as well as crucial implications for the management of malignant pleural effusion (MPE). Indwelling pleural catheters have shown good symptom relief for patients with NEL; hence, identifying patients early in their disease is vital. With the inability of the lung to achieve pleural apposition following thoracentesis and the formation of a hydropneumothorax, traditionally, chest X-ray and clinical symptoms have been used to make the diagnosis following thoracentesis. It is our aim to investigate whether ultrasound measurement of lung movement during respiration can predict NEL before thoracentesis, thereby aiding clinicians in their planning for the optimal treatment of affected patients. Methods: A total of 49 patients were consecutively included in a single-centre trial performed at a pleural clinic. Patients underwent protocolled ultrasound assessment pre-thoracentesis with measurements of lung and diaphragm movement and shear wave elastography measurements of the pleura and pleural effusion at the planned site of thoracentesis. Results: M-mode measurements of lung movement provided the best diagnostic ROC-curve results, with an AUC of 0.81. Internal validity showed good results utilising the calibration belt test and Brier test. Conclusion: M-mode measurement of lung movement shows promise in diagnosing NEL before thoracentesis in patients with known or suspected MPE. A validation cohort is needed to confirm the results. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Digital radiography: Optimization of image quality and dose using multi-frequency software" in the December 2013 issue.

Objectives: Transcatheter aortic valve implantation (TAVI) is an established treatment for high-grade aortic valve stenosis in patients found unfit for open heart surgery. The method may cause cardiac conduction disorders requiring permanent pacemaker (PPM) implantation, and the long-term effect of PPM implantation remains ambiguous. Design One hundred sixty-eight patients who underwent TAVI from 2008 to 2012 were included. Patient characteristics, ECGs and PPM data were collected through medical records. Kaplan-Meier plots and Cox regression analysis were performed.Results: Forty subjects were excluded, leaving 128 patients for final inclusion. 41 (32%) received a PPM (mean age 82 vs. 80 in patients without PPM, p = .06) within 30 days of the TAVI procedure. Median follow-up was ∼4 years and 37 (29%) died. One-year mortality was 14% for non-PPM patients vs. 2% in PPM patients, and mortality at 5yrs 70% vs. 54%, respectively. Kaplan-Meier survival analysis showed higher mortality in patients without PPM (p = .008). In multivariate survival analysis significant variables were: No PPM (HR 2.6; CI 1.1-6.2; p = .03), chronic obstructive pulmonary disease (HR 2.4; CI 1.2-5.0; p = .02) and either pre- or post-procedural chronic or paroxystic atrial fibrillation (HR 2.3; CI 1.2-4.7; p= .02).Conclusion: TAVI-patients with a PPM had better survival than patients in whom a PPM was not implanted. [ABSTRACT FROM AUTHOR]

The increasing emergence of predictive markers for different treatments in the same patient population allows us to define stratified treatment strategies. We consider randomized clinical trials that compare a standard treatment with a new stratified treatment strategy that divides the study population into subgroups receiving different treatments. Because the new strategy may not be beneficial in all subgroups, we consider in this paper an intermediate approach that establishes a treatment effect in a subset of patients built by joining several subgroups. The approach is based on the simple idea of selecting the subset with minimal p-value when testing the subset-specific treatment effects. We present a framework to compare this approach with other approaches to select subsets by introducing three performance measures. The results of a comprehensive simulation study are presented, and the relative merits of the various approaches are discussed. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Coronary computed tomography angiography (CCTA) requires high spatial and temporal resolution, increased low contrast resolution for the assessment of coronary artery stenosis, plaque detection, and/or non-coronary pathology. Therefore, new reconstruction algorithms, particularly iterative reconstruction (IR) techniques, have been developed in an attempt to improve image quality with no cost in radiation exposure. Purpose: To evaluate whether adaptive statistical iterative reconstruction (ASIR) enhances perceived image quality in CCTA compared to filtered back projection (FBP). Material and Methods: Thirty patients underwent CCTA due to suspected coronary artery disease. Images were reconstructed using FBP, 30% ASIR, and 60% ASIR. Ninety image sets were evaluated by five observers using the subjective visual grading analysis (VGA) and assessed by proportional odds modeling. Objective quality assessment (contrast, noise, and the contrast-to-noise ratio [CNR]) was analyzed with linear mixed effects modeling on log-transformed data. The need for ethical approval was waived by the local ethics committee as the study only involved anonymously collected clinical data. Results: VGA showed significant improvements in sharpness by comparing FBP with ASIR, resulting in odds ratios of 1.54 for 30% ASIR and 1.89 for 60% ASIR (P = 0.004). The objective measures showed significant differences between FBP and 60% ASIR (P < 0.0001) for noise, with an estimated ratio of 0.82, and for CNR, with an estimated ratio of 1.26. Conclusion: ASIR improved the subjective image quality of parameter sharpness and, objectively, reduced noise and increased CNR. [ABSTRACT FROM AUTHOR]